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Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer

Owatari, Satsuki, Akune, Satoshi, Komatsu, Masaharu, Ikeda, Ryuji, Firth, Stephen, Che, Xiao-Fang, Yamamoto, Masatatsu, Tsujikawa, Kazutake, Kitazono, Masaki, Ishizawa, Takashi, Takeuchi, Toru, Aikou, Takashi, Mercer, Julian, Akiyama, Shin-ichi and Furukawa, Tatsuhiko 2007, Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer, Cancer research, vol. 67, no. 10, pp. 4860-4868, doi: 10.1158/0008-5472.CAN-06-3096.

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Title Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer
Author(s) Owatari, Satsuki
Akune, Satoshi
Komatsu, Masaharu
Ikeda, Ryuji
Firth, Stephen
Che, Xiao-Fang
Yamamoto, Masatatsu
Tsujikawa, Kazutake
Kitazono, Masaki
Ishizawa, Takashi
Takeuchi, Toru
Aikou, Takashi
Mercer, Julian
Akiyama, Shin-ichi
Furukawa, Tatsuhiko
Journal name Cancer research
Volume number 67
Issue number 10
Start page 4860
End page 4868
Publisher American Association for Cancer Research
Place of publication Philadelphia, Pa.
Publication date 2007-05-15
ISSN 0008-5472
1538-7445
Keyword(s) 7 ethyl 10 hydroxycamptothecin
antineoplastic agent
adenocarcinoma
adenosine triphosphatases
cation transport proteins
Summary We and others have shown that the copper transporters ATP7A and ATP7B play a role in cellular resistance to cisdiaminedichloroplatinum (II) (CDDP).  In this study, we found that ATP7A transfection of Chinese hamster ovary  cells (CHOK1) and fibroblasts isolated from Menkes disease patients  enhanced resistance not only to CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7-ethyl-10- hydroxy-camptothecin (SN-38),  etoposide, doxorubicin, mitoxantron, and 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A preferentially localized
doxorubicin fluorescence to the Golgi apparatus in contrast to the more intense nuclear staining of doxorubicin in the parental cells. Brefeldin A   partially and monensin completely altered the distribution of doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the uptake of SN-38 in membrane vesicles. These findings strongly suggested that   ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi network has an important role of ATP7A-related drug resistance. ATP7A was expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the adjacent normal epithelium. Using the histoculture drug response assay that is useful for the prediction of drug sensitivity of clinical cancers, ATP7A-expressing colon cancer cells were significantly more  resistant to SN-38 than ATP7Anegative cells. Thus, ATP7A confers  resistance to various anticancer agents on cancer cells and might be a good index of drug resistance in clinical colon cancers.
Language eng
DOI 10.1158/0008-5472.CAN-06-3096
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2007, American Association for Cancer Research
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007141

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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